Abstract
Background/objective: Subarachnoid hemorrhage (SAH) is a devastating neurologic event for which markers
to assess poor outcome are needed. Elevated cerebrospinal fluid (CSF) protein may
result from inflammation and blood-brain barrier (BBB) disruption that occurs during
SAH. We sought to determine if CSF protein level is associated with functional outcome
after SAH. Methods: We prospectively collected single-center demographic and clinical data for consecutive
patients admitted with spontaneous SAH. Inclusion required an external ventricular
drain and daily CSF protein and cellular counts starting within 48 hours of symptom
onset and extending through 7 days after onset. Seven-day average CSF protein was
determined from daily measured values after correcting for contemporaneous CSF red
blood cell (RBC) count. Three-month functional outcome was assessed by telephone interview
with good outcome defined as modified Rankin score 0-3. Variables univariately associated
with outcome at P less than .25 and measures of hemorrhage volume were included for binary logistic
regression model development. Results: The study included 130 patients (88% aneurysmal SAH, 69% female, 54.8 ± 14.8 years,
Glasgow Coma Scale [GCS] 14 [7-15]). Three-month outcome assessment was complete in
112 (86%) patients with good functional outcome in 74 (66%). CSF protein was lower
in good outcome (35.3 [20.4-49.7] versus 80.5 [40.5-115.5] mg/dL; P < .001). CSF protein was not associated with cerebral vasospasm, but delayed radiographic
infarction on 3 to 12-month neuroimaging was associated with higher CSF protein (46.3
[32.0-75.0] versus 30.2 [20.4-47.8] mg/dL; P = .023). Good 3-month outcome was independently associated with lower CSF protein
(odds ratios [OR] .39 [.23-.70] for 75th versus 25th percentile of protein; P = .001) and higher admission GCS (OR 1.23 [1.10-1.37] for good outcome per GCS point
increase; P < .001). Parenchymal hematoma predicted worse outcome (OR 6.31 [1.58-25.25]; P = .009). Results were similar after excluding nonaneurysmal SAH and after including
CSF RBC count, CT score, and intraventricular hemorrhage volume in models. Conclusions: Elevated average CSF protein is associated with poor outcome after spontaneous SAH.
Further research should investigate if elevated CSF protein identifies patients in
whom mechanisms such as BBB disruption contribute to poor outcome.
Key Words
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Article info
Publication history
Published online: January 13, 2020
Accepted:
December 13,
2019
Received in revised form:
December 10,
2019
Received:
October 19,
2019
Footnotes
Funding: Dr. Nadkarni receives support from National Institutes of Neurological Disorders and Stroke Research Education grant R25 NS070695. Dr. Maas receives support from National Institutes of Health grant K23 NS092975. Dr. Naidech receives support from Agency for Healthcare Research and Quality grant K18 HS023437. Dr. Liotta receives support from the National Institutes of Health National Center for Advancing Translational Sciences grant KL2TR001424 and the National Institute of Health grant L30 NS098427. Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences grant UL1 TR000150. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Agency for Healthcare Research and Quality.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104605
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© 2019 Elsevier Inc. All rights reserved.
